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Translational Research: the Journal of Laboratory and Clinical Medicine

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https://www.readbyqxmd.com/read/28644958/translating-cancer-epigenomics-into-the-clinic-focus-on-lung-cancer
#1
REVIEW
Josep Mari-Alexandre, Angel Diaz-Lagares, Maria Villalba, Oscar Juan, Ana B Crujeiras, Alfonso Calvo, Juan Sandoval
Epigenetic deregulation is increasingly being recognized as a hallmark of cancer. Recent studies have identified many new epigenetic biomarkers, some of which are being introduced into clinical practice for diagnosis, molecular classification, prognosis or prediction of response to therapies. O-6-methylguanine-DNA methyltransferase gene is the most clinically advanced epigenetic biomarker as it predicts the response to temozolomide and carmustine in gliomas. Therefore, epigenomics may represent a novel and promising tool for precision medicine, and in particular, the detection of epigenomic biomarkers in liquid biopsies will be of great interest for monitoring diseases in patients...
June 2, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28641075/postconditioning-with-intralipid-emulsion-protects-against-reperfusion-injury-in-postinfarct-remodeled-rat-hearts-by-activation-of-ros-akt-erk-signaling
#2
Michael Zaugg, Phing-How Lou, Eliana Lucchinetti, Manoj Gandhi, Alexander S Clanachan
The clinically used lipid emulsion Intralipid (ILE) reduces ischemia reperfusion injury in healthy rodent hearts. We tested whether ILE is cardioprotective in postinfarct remodeled hearts. Postinfarct remodeled and sham Sprague-Dawley rat hearts were perfused in working mode and subjected to ischemia (15 minutes) and reperfusion (30 minutes). Left ventricular (LV) work was measured in hearts that were untreated or that received ILE (1%) postconditioning administered at the onset of reperfusion, or the reactive oxygen species (ROS) scavenger N-(2-mercaptopropionyl)-glycine (10 μM) alone or in combination with ILE...
June 1, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28641074/development-of-novel-antigen-receptors-for-car-t-cell-therapy-directed-toward-solid-malignancies
#3
REVIEW
David Chen, James Yang
Development of chimeric antigen receptor (CAR) T cells have led to remarkable successes in the treatment of B-cell malignancies with anti-CD19 CAR. Here we discuss the development of novel antigen receptors for use in solid malignancies with respect to target antigens, receptor design, and T cell manipulations.
June 1, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28586635/tin-protoporphyrin-activates-the-oxidant-dependent-nrf2-cytoprotective-pathway-and-mitigates-acute-kidney-injury
#4
Ali C M Johnson, Jeff J Delrow, Richard A Zager
Tin protoporphyrin (SnPP), a heme oxygenase (HO) inhibitor, can paradoxically protect against diverse forms of acute kidney injury (AKI). This study sought potential underlying mechanisms. CD-1 mice received intravenous SnPP, followed 4-18 hours later by a variety of renal biochemical, histologic, and genomic assessments. Renal resistance to ischemic-reperfusion injury (IRI) was also sought. SnPP was rapidly taken up by kidney and was confined to proximal tubules. Transient suppression of renal heme synthesis (decreased δ aminolevulinic acid synthase expression), a 2...
May 19, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28583767/lxr-dependent-regulation-of-macrophage-specific-reverse-cholesterol-transport-is-impaired-in-a-model-of-genetic-diabesity
#5
Teresa L Errico, Karen Alejandra Méndez-Lara, David Santos, Núria Cabrerizo, Lucía Baila-Rueda, Jari Metso, Ana Cenarro, Eva Pardina, Albert Lecube, Matti Jauhiainen, Julia Peinado-Onsurbe, Joan Carles Escolà-Gil, Francisco Blanco-Vaca, Josep Julve
Diabesity and fatty liver have been associated with low levels of high-density lipoprotein cholesterol, and thus could impair macrophage-specific reverse cholesterol transport (m-RCT). Liver X receptor (LXR) plays a critical role in m-RCT. Abcg5/g8 sterol transporters, which are involved in cholesterol trafficking into bile, as well as other LXR targets, could be compromised in the livers of obese individuals. We aimed to determine m-RCT dynamics in a mouse model of diabesity, the db/db mice. These obese mice displayed a significant retention of macrophage-derived cholesterol in the liver and reduced fecal cholesterol elimination compared with nonobese mice...
May 18, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28554003/opioids-and-opioid-receptors-orchestrate-wound-repair
#6
Ying Wang, Mihir Gupta, Tasneem Poonawala, Mariya Farooqui, Yunfang Li, Fei Peng, Sheldon Rao, Michael Ansonoff, John E Pintar, Kalpna Gupta
We have previously shown that topical opioids including morphine and its congeners promote healing of full thickness ischemic wounds in rats. We examined the contribution of mu opioid receptor (MOPr)-mediated healing of full thickness ischemic wounds using MOPr and delta or kappa opioid receptor knockout (KO) mice. Wound closure in the early (day 5) as well as later phases was delayed in topical morphine or PBS-treated MOPr-KO mice compared with reciprocal treatments of wounds in wild-type (WT) mice. MOPr expression was significantly upregulated at 30 min in the wound margins and colocalized with wound margins and vasculature in the epidermal and dermal layers of the skin...
May 18, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28549851/identification-of-pathway-based-prognostic-gene-signatures-in-patients-with-multiple-myeloma
#7
Mohamad Zamani-Ahmadmahmudi, Shahreyar Dabiri, Nadia Nadimi
Molecular profiling is used to extract prognostic gene signatures in different cancers such as multiple myeloma (MM), which is the second most common hematological malignancy. In this study, we utilized gene expression profiles to find biological pathways that could efficiently predict survival time in patients with MM. Four data sets-namely GSE2658 (559 samples), GSE9782 (264 samples), GSE6477 (147 samples), and GSE57317 (55 samples)-were employed. GSE2658 was used as a training data set and the others as validation data sets...
May 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28528915/sphingosine-metabolism-as-a-therapeutic-target-in-cutaneous-melanoma
#8
REVIEW
Mohammed Dany
Melanoma is by far the most aggressive type of skin cancer with a poor prognosis in its advanced stages. Understanding the mechanisms involved in melanoma pathogenesis, response, and resistance to treatment has gained a lot of attention worldwide. Recently, the role of sphingolipid metabolism has been studied in cutaneous melanoma. Sphingolipids are bioactive lipid effector molecules involved in the regulation of various cellular signaling pathways such as inflammation, cancer cell proliferation, death, senescence, and metastasis...
May 4, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28506697/inflammation-and-hemostasis-in-older-octogenarians-implication-in-5-year-survival
#9
Judit Cubedo, Teresa Padró, Francesc Formiga, Assumpta Ferrer, Glòria Padrós, Esther Peña, Lina Badimon
Social changes and medical advances have increased longevity, but the conditions governing healthy vs unhealthy cardiovascular (CV) aging are not fully known. Factors beyond classical CV risk factors may have an important unrecognized value. We sought to identify proteins differentially expressed in healthy octogenarians (HOs) without a history of cardiovascular disease (CVD) and preserved functional and cognitive state compared with octogenarians with a history of CVD and cognitive decline (UHOs) using a systems biology approach, and investigated how these proteins relate to CV mortality at 5-year follow-up...
April 26, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28506696/current-approaches-for-avoiding-the-limitations-of-circulating-tumor-cells-detection-methods-implications-for-diagnosis-and-treatment-of-patients-with-solid-tumors
#10
REVIEW
Artur Kowalik, Magdalena Kowalewska, Stanisław Góźdź
Eight million people die of cancer each year and 90% of deaths are caused by systemic disease. Circulating tumor cells (CTCs) contribute to the formation of metastases and thus are the subject of extensive research and an abiding interest to biotechnology and pharmaceutical companies. Recent technological advances have resulted in greatly improved CTC detection, enumeration, expansion, and culture methods. However, despite the fact that nearly 150 years have passed since the first detection and description of CTCs in human blood and enormous technological progress that has taken place in this field, especially within the last decade, few CTC detection methods have been approved for routine clinical use...
April 26, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28502785/car-t-cell-therapy-for-lung-cancer-and-malignant-pleural-mesothelioma
#11
REVIEW
Masha Zeltsman, Jordan Dozier, Erin McGee, Daniel Ngai, Prasad S Adusumilli
Immunotherapy is a promising field that harnesses the power of the immune system as a therapeutic agent for cancer treatment. Beneficial outcomes shown in patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) with relatively higher tumor-infiltrating T cells, combined with impressive responses obtained in a cohort of patients with NSCLC following checkpoint blockade therapy, lays a strong foundation to promote effector immune responses in these patients. One such approach being investigated is administration of tumor antigen-targeted T cells with transduction of a chimeric antigen receptor (CAR)...
April 26, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28482173/evaluation-of-a-combination-tumor-treatment-using-thermo-triggered-liposomal-drug-delivery-and-carbon-ion-irradiation
#12
Daisuke Kokuryo, Ichio Aoki, Eiji Yuba, Kenji Kono, Sadahito Aoshima, Jeff Kershaw, Tsuneo Saga
The combination of radiotherapy with chemotherapy is one of the most promising strategies for cancer treatment. Here, a novel combination strategy utilizing carbon ion irradiation as a high-linear energy transfer (LET) radiotherapy and a thermo-triggered nanodevice is proposed, and drug accumulation in the tumor and treatment effects are evaluated using magnetic resonance imaging relaxometry and immunohistology (Ki-67, n = 15). The thermo-triggered liposomal anticancer nanodevice was administered into colon-26 tumor-grafted mice, and drug accumulation and efficacy was compared for 6 groups (n = 32) that received or did not receive the radiotherapy and thermo trigger...
April 21, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28438520/urinary-long-noncoding-rnas-in-nonmuscle-invasive-bladder-cancer-new-architects-in-cancer-prognostic-biomarkers
#13
REVIEW
Daniela Terracciano, Matteo Ferro, Sara Terreri, Giuseppe Lucarelli, Carolina D'Elia, Gennaro Musi, Ottavio de Cobelli, Vincenzo Mirone, Amelia Cimmino
Several reports over the last 10 years provided evidence that long noncoding RNAs (lncRNAs) are often altered in bladder cancers. lncRNAs are longer than 200 nucleotides and function as important regulators of gene expression, interacting with the major pathways of cell growth, proliferation, differentiation, and survival. A large number of lncRNAs has oncogenic function and is more expressed in tumor compared with normal tissues. Their overexpression may be associated with tumor formation, progression, and metastasis in a variety of tumors including bladder cancer...
April 7, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28427903/atrial-fibrillation-is-associated-with-hypermethylation-in-human-left-atrium-and-treatment-with-decitabine-reduces-atrial-tachyarrhythmias-in-spontaneously-hypertensive-rats
#14
R Doñate Puertas, E Meugnier, C Romestaing, C Rey, E Morel, J Lachuer, N Gadot, A Scridon, C Julien, F Tronc, B Chapuis, C Valla, A Janin, L Pirola, A Méjat, S Rome, P Chevalier
Atrial fibrillation (AF) is the most common cardiac arrhythmia. As the molecular mechanisms underlying the pathology are largely unknown, this cardiac arrhythmia remains difficult to treat. To identify specific molecular actors involved in AF, we have performed a transcriptomic analysis on left atrium (LA) from patients with valvular heart disease with or without AF. We showed that 1627 genes had altered basal expression level in LA tissue of AF patients compared with the control group. The significantly enriched gene ontology biological process "anatomical structure morphogenesis" contained the highest number of genes in line with changes in structure that occur when the human heart remodels following AF development (ie, LA dilatation and interstitial fibrosis)...
March 30, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28552218/epigenetics-and-type-1-diabetes-mechanisms-and-translational-applications
#15
REVIEW
Alberto Zullo, Linda Sommese, Gianfranco Nicoletti, Francesco Donatelli, Francesco P Mancini, Claudio Napoli
Type 1 diabetes (T1D) is an irreversible degenerative disease with severe complications such as heart disease, nephropathy, neuropathy, and retinopathy. Although exogenous insulin administration is a life-saving therapy, it does not cure the disease. This review addresses the epigenetic mechanisms responsible for the development of T1D and discusses epigenetic-based strategies for prevention and treatment of the disease. We describe novel epigenetic biomarkers for the identification of susceptible individuals and the establishment of innovative therapies with epidrugs and cell therapy to regenerate the lost β-cells...
July 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28363084/the-metabolic-syndrome-induces-early-changes-in%C3%A2-the-swine-renal-medullary-mitochondria
#16
Alfonso Eirin, John R Woollard, Christopher M Ferguson, Kyra L Jordan, Hui Tang, Stephen C Textor, Amir Lerman, Lilach O Lerman
The metabolic syndrome (MetS) is associated with nutrient surplus and kidney hyperfiltration, accelerating chronic renal failure. Mitochondria can be overwhelmed by substrate excess, leading to inefficient energy production and thereby tissue hypoxia. Mitochondrial dysfunction is emerging as an important determinant of renal damage, but whether it contributes to MetS-induced renal injury remains unknown. We hypothesized that early MetS induces kidney mitochondrial abnormalities and dysfunction, which would be notable in the vulnerable renal medulla...
June 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28336465/smoking-and-the-risk-of-type-2-diabetes
#17
REVIEW
Judith Maddatu, Emily Anderson-Baucum, Carmella Evans-Molina
Despite accumulating evidence demonstrating strong epidemiologic and mechanistic associations between cigarette smoking, hyperglycemia, and the development of type 2 diabetes, tobacco abuse has not been uniformly recognized as a modifiable risk factor in diabetes prevention or screening strategies. In this review, we highlight population-based studies that have linked cigarette smoking with an increased risk of type 2 diabetes and summarize clinical and preclinical studies offering insight into mechanisms through which cigarette smoking and nicotine exposure impact body composition, insulin sensitivity, and pancreatic β cell function...
June 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28284670/vascular-precursor-cells-in-tissue-injury-repair
#18
REVIEW
Xin Shi, Weihong Zhang, Liya Yin, William M Chilian, Jessica Krieger, Ping Zhang
Vascular precursor cells include stem cells and progenitor cells giving rise to all mature cell types in the wall of blood vessels. When tissue injury occurs, local hypoxia and inflammation result in the generation of vasculogenic mediators which orchestrate migration of vascular precursor cells from their niche environment to the site of tissue injury. The intricate crosstalk among signaling pathways coordinates vascular precursor cell proliferation and differentiation during neovascularization. Establishment of normal blood perfusion plays an essential role in the effective repair of the injured tissue...
June 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28130064/cardiovascular-consequences-of-metabolic-syndrome
#19
REVIEW
Johnathan D Tune, Adam G Goodwill, Daniel J Sassoon, Kieren J Mather
The metabolic syndrome (MetS) is defined as the concurrence of obesity-associated cardiovascular risk factors including abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, decreased HDL cholesterol, and/or hypertension. Earlier conceptualizations of the MetS focused on insulin resistance as a core feature, and it is clearly coincident with the above list of features. Each component of the MetS is an independent risk factor for cardiovascular disease and the combination of these risk factors elevates rates and severity of cardiovascular disease, related to a spectrum of cardiovascular conditions including microvascular dysfunction, coronary atherosclerosis and calcification, cardiac dysfunction, myocardial infarction, and heart failure...
May 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28087261/dna-aptamer-probes-for-detection-of-estrogen-receptor-%C3%AE-positive-carcinomas
#20
Arghya Sett, Bibhuti Bhusan Borthakur, Jagannath Dev Sharma, Amal Chandra Kataki, Utpal Bora
Estrogen receptor alpha (ERα) also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1) is a ligand-activated transcription factor. It is an important biomarker for breast cancer metastasis. In the present study, we report a novel DNA aptamer candidate against estrogen receptor (ER) alpha structure. The enriched aptamer candidate was obtained after 14 iterative cycles of in vitro protein-SELEX process. Isothermal calorimetry study suggests the nanomolar sensitivity of the candidate ER_Apt1 to its target protein...
May 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
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